These authors contributed equally to this work.
Metallothionein 1 h tumour suppressor activity in prostate cancer is mediated by euchromatin methyltransferase 1
Article first published online: 13 MAY 2013
Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 230, Issue 2, pages 184–193, June 2013
How to Cite
Han, Y.-C., Zheng, Z.-L., Zuo, Z.-H., Yu, Y. P., Chen, R., Tseng, G. C., Nelson, J. B. and Luo, J.-H. (2013), Metallothionein 1 h tumour suppressor activity in prostate cancer is mediated by euchromatin methyltransferase 1. J. Pathol., 230: 184–193. doi: 10.1002/path.4169
No conflicts of interest were declared.
- Issue published online: 13 MAY 2013
- Article first published online: 13 MAY 2013
- Accepted manuscript online: 25 JAN 2013 10:20AM EST
- Manuscript Accepted: 25 DEC 2012
- Manuscript Revised: 28 NOV 2012
- Manuscript Received: 25 JUL 2012
- prostate cancer;
- histone methylation
Metallothioneins (MTs) are a group of metal binding proteins thought to play a role in the detoxification of heavy metals. Here we showed by microarray and validation analyses that MT1h, a member of MT, is down-regulated in many human malignancies. Low expression of MT1h was associated with poor clinical outcomes in both prostate and liver cancer. We found that the promoter region of MT1h was hypermethylated in cancer and that demethylation of the MT1h promoter reversed the suppression of MT1h expression. Forced expression of MT1h induced cell growth arrest, suppressed colony formation, retarded migration, and reduced invasion. SCID mice with tumour xenografts with inducible MT1h expression had lower tumour volumes as well as fewer metastases and deaths than uninduced controls. MT1h was found to interact with euchromatin histone methyltransferase 1 (EHMT1) and enhanced its methyltransferase activity on histone 3. Knocking down of EHMT1 or a mutation in MT1h that abrogates its interaction with EHMT1 abrogated MT1h tumour suppressor activity. This demonstrates tumour suppressor activity in a heavy metal binding protein that is dependent on activation of histone methylation. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.